Potential Therapeutic Application of Regulatory T Cells in Diabetes Mellitus Type 1.

The autoimmune reaction against the beta cells of the pancreatic islets in type 1 diabetes mellitus (T1DM) patients is active in prediabetes and during the development of the clinical manifestation of T1DM, but it decreases within a few years of the clinical manifestation of this disease. A key role in the pathogenesis of T1DM is played by regulatory T cell (Treg) deficiency or dysfunction. Immune interventions, such as potential therapeutic applications or the induction of the Treg-cell population in T1DM, will be important in the development of new types of treatment. The aim of this study was to evaluate innovative immune interventions as treatments for T1DM. After an evaluation of full-length papers from the PubMed database from 2010 to 2021, 20 trials were included for the final analysis. The analysis led to the following conclusions: Treg cells play an important role in the limitation of the development of T1DM, the activation or application of Tregs may be more effective in the early stages of T1DM development, and the therapeutic use of Treg cells in T1DM is promising but requires long-term observation in a large group of patients.

Interleukin 22 and 6 serum concentrations decrease under long-term biologic therapy in psoriasis.

INTRODUCTION: Psoriasis, affecting approximately 2% of the worldwide population, is a chronic, inflammatory skin disease in which overexpression of proinflammatory cytokines is observed. Most of the available data on the influence of antipsoriatic therapy on the cytokine serum concentration are inconsistent and based on short-term observations. AIM: To evaluate the influence of long-term biologic therapy with tumor necrosis factor α (TNF-α) blockers (adalimumab, etanercept, infliximab) and IL-12/23 inhibitor (ustekinumab) on the level of IL-6, IL-22 in the sera of patients with psoriasis. MATERIAL AND METHODS: Blood samples were collected from 42 psoriatic patients in order to determine IL-6 and IL-22 serum concentrations prior to and at the 3rd, 12th, 24th and 36th month of biologic therapy. Psoriasis Activity and Severity Index (PASI) was assessed at the same time points. The control group consisted of 30 sex- and age-matched healthy volunteers. RESULTS: Mean PASI index at baseline was 14.49 ±3.69 and decreased significantly until the end of the observation. Mean IL-6 serum concentration decreased significantly in all study groups (p < 0.05). A statistically significant decrease in IL-22 concentrations was demonstrated during the treatment with adalimumab and infliximab but not etanercept or ustekinumab. CONCLUSIONS: According to obtained results, IL-6 and IL-22 serum concentration may be an accurate marker of response to antipsoriatic therapy, even though not correlated with PASI index. Biologic therapy in psoriasis allows for long-term clinical improvement expressed not only by the remission of skin lesions, but also by lowering serum concentrations of pro-inflammatory interleukins.

Ingenol mebutate treatment in actinic keratosis - clinical effectiveness and potential side effects.

INTRODUCTION: Actinic keratosis is a common skin disease that occurs in response to prolonged exposure to ultraviolet radiation. This problem affects up to 60% of the population over 40 years of age. Actinic keratosis is considered to be a precancerous lesion leading to squamous cell carcinoma (SCC). The new therapeutic option for the treatment of actinic keratosis is ingenol mebutate gel (0.015%, 0.05%). AIM: Retrospective evaluation of response and potential side effects of ingenol mebutate treatment in clinical practice. MATERIAL AND METHODS: Eight patients with actinic keratosis lesions on the face or scalp self-applied a 0.015% gel for 3 consecutive days on the 25 cm2 marked area. They were assessed at baseline and on day 4, 7, 14 and 57. RESULTS: All patients on day 57 presented a complete absence of AK lesions in the area of ingenol mebutate application. No adverse events were observed. CONCLUSIONS: Our study shows that ingenol mebutate is highly efficacious field treatment for actinic keratosis.

Epidemiology of type 1 diabetes in Polish children: A multicentre cohort study.

BACKGROUND: The incidence of childhood type 1 diabetes (T1D) varies greatly between populations, and the estimates and/or predictions of the rates would aid in adequate planning of health care resources. The study's aim was to assess the incidence of T1D in the paediatric population of eastern and central Poland. METHODS: In this cohort study covering the period from January 2010 to December 2014, data were collected for children and adolescents below 18 years of age with newly diagnosed T1D living in eastern and central Poland. A total of 2174 children were included in the analysis. The population estimates were from the Central Statistical Office of Poland. RESULTS: Overall, the annual incidence of T1D increased from 12.84/100,000 in 2010 to 18.46/100,000 in 2014 with the incidence rate (IR) ratio of 1.5 (an increase in the IR by 12.7% per year over 5 years). The lowest increase in the IR by 7.1% per year was seen in 15 to 17-year-olds. In the urban population (age 0-17 years), the overall incidence rate was significantly higher than in subjects from rural communities (P < .02). The incidence of T1D in rural areas was significantly higher (p = .004) in voivodeships of higher population density. Such dependence was not observed in urban areas. CONCLUSIONS: The incidence of T1D in children living in eastern and central Poland increased 1.5-fold over the 5-year observation period with the highest rise in 10 to 14-year-olds and significantly higher rates in urban children compared with their peers living in rural areas.

High incidence of diabetic ketoacidosis at diagnosis of type 1 diabetes among Polish children aged 10-12 and under 5 years of age: A multicenter study.

AIM: Despite its characteristic symptoms, type 1 diabetes (T1D) is still diagnosed late causing the development of diabetic ketoacidosis (DKA). The aim of this study was to estimate the incidence of DKA and factors associated with the development of acidosis at T1D recognition in Polish children aged 0-17. METHODS: The study population consisted of 2100 children with newly diagnosed T1D in the years 2010-2014 in 7 hospitals in eastern and central Poland. The population living in these areas accounts for 35% of the Polish population. DKA was defined as a capillary pH < 7.3, blood glucose > 11 mmol/L. The analyzed data included age, sex, diabetes recognition, pH, glycated hemoglobin (HbA1c), fasting C-peptide, and body mass index standard deviation score (BMI-SDS). RESULTS: We observed DKA in 28.6% of children. There were 2 peaks in DKA occurrence: in children <5 years of age (33.9%) and aged 10-12 (34%). The highest incidence of DKA was noted in children aged 0-2 (48.4%). In the group with DKA, moderate and severe DKA occurred in 46.7% of children. Girls and children <2 years of age were more prone to severe DKA. The multiple logistic regression analysis showed the following factors associated with DKA: age (P = .002), fasting C-peptide (P = .0001), HbA1c (P = .0001), no family history of T1D (P = .0001), and BMI-SDS (P = .0001). CONCLUSIONS: The incidence of DKA is high and remained unchanged over the last 5 years. Increasing the awareness of symptoms of DKA is recommended among children <5 years of age (especially <2 years of age) and aged 10-12. Children <2 years of age and girls were at the highest risk of severe DKA.

Can biologic treatment induce cutaneous focal mucinosis?

Skin mucinosis is a rare skin disease which clinically manifests as firm papules and waxy nodules. We report a case of a 66-year-old female psoriatic patient who developed skin mucinosis during biological therapy. Because of a previous lack of response to the local and conventional systemic treatment of psoriasis, the patient received biological therapy (infliximab from June 2008 to May 2009 - initial clinical improvement and loss of treatment effectiveness in the 36(th) week of the therapy; adalimumab from June 2009 to January 2010 - lack effectiveness; ustekinumab from March 2012 to the present). Throughout 2 months we observed a manifestation of the skin mucinosis as well-demarcated, yellow and brown, papulo-nodular lesions of 5-10 mm in diameter, localized on the back. Histopathological examination with alcian blue staining demonstrated mucin deposits in the dermis. On the basis of clinical and histopathological findings, the diagnosis of cutaneous focal mucinosis was established. We present the case because of the extremely rare occurrence of the disease. Scarce literature and data suggest that there is an association between focal mucinosis and thyroid dysfunction, as well as possible adverse effects of biological therapy with TNF-α antagonists.

Multiple symmetrical lipomatosis: A literature review and case report of a patient with Madelung's disease.

<b><br>Introduction:</b> Madelung's disease is a rare condition characterised by the symmetric growth of fatty tumours (lipomas) around the neck, shoulders, upper arms and trunk.</br> <b><br>Case report:</b> We present a description of a male patient with extensive adipose tissue overgrowth around the neck. Once the possibility of malignancy was excluded, the patient's history and clinical and radiological findings led to the diagnosis of Madelung's disease. A two-stage surgery was planned and the patient underwent lipectomy of the lipomas around the neck.</br> <b><br>Conclusions:</b> This article analyses the clinical data with Madelung's disease; discusses its aetiology, clinical manifestations, diagnosis and treatment methods; and provides help with clinical diagnosis and treatment.</br>.

Lower percentages of natural killer cells in children with type 1 diabetes and their siblings.

INTRODUCTION: One of the most common children's endocrine and autoimmune diseases in the world is type 1 diabetes mellitus (T1DM). The incidence of type 1 diabetes is constantly increasing, and according to current estimates, the number of children with T1DM in the world has exceeded 542,000. There are 3 main components emphasized in the pathogenesis: genetic and environmental factors, and the patient's immune system. Many publications have confirmed the role of natural killer cells (NK) in the pathogenesis of type 1 diabetes and other autoimmune diseases. AIM: The aim of the study was to evaluate the population of NK cells and pancreatic ß cell autoantibodies in a group of children with T1DM and their healthy siblings in comparison with children from families with no history of autoimmune diseases. MATERIAL AND METHODS: The research included 76 children with T1DM, 101 children from the sibling group, and 30 children from the control group. Peripheral blood was analysed on a FACSCalibur flow cytometer (Becton Dickinson) to evaluate the NK cell population. The results were presented as the percentage of NK cells among lymphocytes. Statistical analysis was performed using STATIS-TICA 10 PL software. RESULTS: The mean percentage of NK cells in children with T1D (10.59 ±5.37) and in the sibling group (11.93 ±5.62) was statistically reduced in comparison to the control group (14.89 ±7.78) in sequence (Student's t -test: t = -3.24; df = 103; p = 0.002) (Stu-dent's t -test: t = -2.30; df = 128; p = 0.02). There was no statistically significant difference in the percentage of NK cells be-tween the group of children with T1DM and their siblings (Student's t -test: t = -1.59; df = 173; p = 0.11). In the group of sib-lings, the younger the child, the lower the reported percentage of NK cells. This relationship was statistically significant (test for the Pearson correlation coefficient t = 3.41; p = 0.0009; r = 0.33). In the group of children with type 1 diabetes, a similar relationship was not found. The concentration of anti-IA2 and anti-Znt8 antibodies was statistically significantly higher in the sibling group compared to the control group (anti-IA2 p = 0.0000001; anti-ZnT8 p = 0.00001), and the concentration of anti-GAD antibodies was comparable in both groups. In the group of children with type 1 diabetes, a positive correlation was demonstrated between the reduced percentage of NK cells and the coexistence of anti-GAD and anti-ZnT8 antibodies (Mann-Whitney U test Z = -2.02; p = 0.04). There was no similar relationship in the group of siblings. CONCLUSIONS: The reduced percentage of NK cells in children with T1DM and in their siblings compared to the control group suggests the role of NK cells in the pathogenesis of T1DM. Genetic predisposition and dysfunction of NK cells probably underlie the pathogenesis of T1DM.

Impact of the COVID-19 Pandemic on Atopic Dermatitis Patients.

Atopic dermatitis (AD) can have a significantly negative impact on quality of life (QoL). The impact of coronavirus disease 2019 (COVID-19) on the AD population is not yet well established. The study comprised 195 patients with diagnosed AD who were asked about their cognitive and preventive behaviors regarding COVID-19 and the accessibility of medical support, including online consultations. Moreover, the patients responded to the self-reported Dermatology Life Quality Index (DLQI) and Hospital Anxiety and Depression Scale (HADS). Most of the patients were worried about being infected with COVID-19. Most of the patients believed that people suffering from skin disease were more prone to be infected with COVID-19 compared with the general population. Most the patients negatively assessed the availability of dermatological treatment during the pandemic. Furthermore, 66.1% of the patients declared using telemedicine. Nearly 50% of patients were discontented with telemedicine, and 1/3 of the patients did not mind the use of telemedicine. AD during the COVID-19 pandemic was associated with a lower overall health rating and life satisfaction and impaired QoL related to mental health in a Polish population. These results provide original information that can be applied in dermatologic patient screenings to evaluate the state of depression and anxiety during the epidemic period.

Thyroid Cancer Risk Factors in Children with Thyroid Nodules: A One-Center Study.

Thyroid nodules are common in the adult population (13%), but in childhood, they are relatively rarely diagnosed (0.2-5%). The risk factors and diagnostic and therapeutic algorithms are well-known and effectively used in adults, but no clear procedures supported by scientific research are available in the pediatric population. Our aim in this study was to identify predictive factors for thyroid cancer in a pediatric population. We retrospectively analyzed 112 children (80 girls and 32 boys, aged 0.6-18 years, with an average group age of 13.4 ± 4.5 years) with thyroid nodules who presented or were referred between 2010 and 2021. A total of 37 children qualified for partial or total thyroidectomy. After histopathological nodule examination, the most common cases were benign lesions in 23 patients (57.5%) and malignant lesions in 14 children (32.5%). Solitary benign thyroid nodules were found in 16 children (40%). Malignancy risk was higher in children with increased nodule diameter (greater than 7 mm; p = 0.018) or hypoechogenic lesions in ultrasound (p = 0.010), with no correlation between increased blood flow in the vessels and tumor diagnosis. The relative risk of developing thyroid cancer for class III was found to be higher in comparison to adults and 11.1 times higher than for classes I and II combined.

AntiTNF-alpha therapy normalizes levels of lipids and adipokines in psoriatic patients in the real-life settings.

Studies have shown that the levels of pro-inflammatory adipokines in patients with psoriasis are higher than in general population. The aim of the study was to investigate the influence of 36-month therapy with TNF-α inhibitors (adalimumab, etanercept, infliximab) on the levels of adipokines (resistin, adiponectin, leptin) and lipids (TG, cholesterol, LDL, HDL) in 37 psoriasis patients and 30 healthy controls. The mean serum concentrations of adiponectin in patients from adalimumab, etanercept and infliximab group were similar to control group (p > 0.05, 142.71, 164.32, 129.35 and 174.44 µg/ml respectively). Resistin levels were higher in patients (p < 0.05, 4.48, 4.53 and 3.39 ng/ml respectively) than in controls (3.05 ng/ml). Mean leptin concentrations were significantly higher (p < 0.05) in the study group than in subjects without psoriasis (428.61, 523.24, 755.27 and 154.10 pg/ml respectively). A significant decrease in the mean resistin concentration was observed under the influence of biological therapy (p < 0.05). Decrease in serum leptin level was noted in etanercept and infliximab groups (p = 0.001 and p = 0.002 respectively). Improvement in all lipidogram parameters was noted in all examined groups (p < 0.05). Results may prove that biologic therapy affects the systemic inflammation associated with psoriasis and this effect persists with long-term therapy.

Seasonal Variation in Month of Diagnosis of Polish Children with Type 1 Diabetes - A Multicenter Study.

AIM: The seasonal variation of incidence of type 1 diabetes (T1D) theory supports the hypothesis that environmental factors play a role in the onset of the disease. The aim of this study is to assess seasonality of month of diagnosis in children with T1D in Poland. MATERIAL AND METHODS: the study group consisted of 2174 children from eastern and central Poland diagnosed with T1D between 2010 and 2014. Analysis was performed in different age groups, based on place of residence (rural/urban area) and depending on sex. RESULTS: We noted significant seasonality in the incidence of T1D with a peak in diagnosis of diabetes in January and the minimum rate in June. A total of 423 (19%) children were diagnosed in the warmest months (June to August with a mean temperature of 16.8°C) compared to 636 (29%) recognised in the coldest months (December to February with a mean temperature of -1.6°C), OR 0.57 95%CI [0.51-0.67], p<0.0001. We noted a more flat seasonal pattern in children 0-4 years of age compared with subjects 5-17 years old with a week correlation of trend comparison between both groups, r=0.69, p=0.001. Similar seasonal variation in the incidence of T1D was noted in children from urban and rural setting. For girls, seasonal pattern peaks were observed one month earlier as compared to boys. CONCLUSIONS: Seasonal variation in incidence of T1D diagnosis of Polish children supports the role of different environmental factors in diabetes onset. The majority of children were diagnosed with diabetes in autumn and winter.

Factors associated with preservation of C-peptide levels at the diagnosis of type 1 diabetes.

AIMS: The level of C-peptide can identify individuals most likely to respond to immune interventions carried out to prevent pancreatic ß-cell damage. The aim of the study was to evaluate factors associated with C-peptide levels at type 1 diabetes (T1D) diagnosis. METHODS: This study included 1098 children aged 2-17 with newly recognized T1D. Data were collected from seven Polish hospitals. The following variables were analyzed: date of birth, fasting C-peptide, HbA1c, sex, weight, height, pH at diabetes onset. RESULTS: A correlation was observed between fasting C-peptide level and BMI-SDS (p = 0.0001), age (p = 0.0001), and HbA1c (p = 0.0001). The logistic regression model revealed that fasting C-peptide ≥0.7 ng/ml at diabetes diagnosis was dependent on weight, HbA1c, pH and sex (p < 0.0001). Overweight and obese children (n = 124) had higher fasting C-peptide (p = 0.0001) and lower HbA1c (p = 0.0008) levels than other subjects. Girls had higher fasting C-peptide (p = 0.036) and higher HbA1c (p = 0.026) levels than boys. CONCLUSION: Obese and overweight children are diagnosed with diabetes at an early stage with largely preserved C-peptide levels. Increased awareness of T1D symptoms as well as improved screening and diagnostic tools are important to preserve C-peptide levels. There are noticeable gender differences in the course of diabetes already at T1D diagnosis.